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Brain & Heart

CASE REPORT
Brain pathology in an infant with PROKR2

microduplication: A case report

1
1
Elvio Della Giustina * , Tiziana Salviato , MariaCristina Davolio ,
2
2
Sabino Pelosi , Luca Fabbiani , Stefania Caramaschi ,
1
1
and Luca Reggiani Bonetti 1
1 Division of Pathology, Maternal-Pediatric and Adult Department of Clinical and Surgical Sciences,
Faculty of Medicine, University of Modena and Reggio Emilia (UNIMORE), Modena, Italy
2 Department of Legal Medicine and Risk Management, Faculty of Medicine, AUSL Modena,
Modena, Italy

Abstract
Overexpression of prokineticins and their receptors is increasingly recognized as a
contributing factor in heart failure and often fatal myocyte necrosis. Activation of
prokineticin pathways is typically triggered by cerebral hypoxia and ischemia, viral
and bacterial infections, inflammatory and immune responses, or energy deprivation
leading to cell apoptosis. However, experimental models have demonstrated that
prokineticin pathway activation can also occur independently due to aberrant
expressions of specific microduplicated/microdeleted genes. Although prokineticins
may play a causal role in cardiac death in adults and children with abnormalities of
accessory pathways between the atria and ventricles, they have never been reported
*Corresponding author: to cause brain injuries, especially in neonates. This report describes an infant born with
Elvio Della Giustina facial dysmorphisms and moderate hypoxic distress at birth but without evidence of
(edellagi@unimore.it) atrioventricular conduction defects, viral or bacterial infections, or severe metabolic
Citation: Giustina ED, Salviato T, dysfunction. Despite these findings, neuropathologic examination following the
Davolio M, et al. Brain pathology infant’s death at 5 months revealed recent necrotic foci in the cerebral cortex and,
in an infant with PROKR2
microduplication: A case report. in particular, older brain lesions with features indicative of metabolic energy failure
Brain & Heart. 2025;3(1):4281. in subcortical structures. Genetic analysis identified a rare prokineticin receptor 2
doi: 10.36922/bh.4281 (PROKR2) gene microduplication, which, in the absence of other identifiable causes,
Received: July 18, 2024 is strongly implicated as a contributing factor in the observed chronic brain lesions.
These findings suggest that PROKR2 gene microduplication may contribute to
Revised: October 13, 2024
unexplained neonatal brain injury, warranting further investigation.
Accepted: November 26, 2024
Published online: December 18, Keywords: Prokineticin receptor 2; Microduplication; Heart failure; Cerebral necrosis;
2024
Cardiac injury
Copyright: © 2024 Author(s).
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution, 1. Background
and reproduction in any medium,
provided the original work is Double-stranded RNA-dependent protein kinases are G-protein-coupled receptors that
properly cited. bind the two small proteins prokineticin 1 (PROK1) and prokineticin 2 (PROK2), which
Publisher’s Note: AccScience play critical roles in various biological functions across multiple tissues. The prokineticin
Publishing remains neutral with receptor 1, encoded in the 2q14 region, is predominantly expressed in human endocrine
regard to jurisdictional claims in
published maps and institutional glands, while prokineticin receptor 2 (PROKR2 or PKR2), encoded in 20p12.3, is most
affiliations. highly expressed in the heart and, to some extent, the brain. In particular, PROK1 shares

Volume 3 Issue 1 (2025) 1 doi: 10.36922/bh.4281